Protein Z (PZ) is a prominent albumin found in the endosperm of barley seeds with a molecular weight of approximately 40 kDa. Its multifaceted functional attributes, including trypsin- and thrombin-inhibiting bioactivities and superior foaming properties, have garnered significant attention in research. Considering the post-translational modifications of PZ natural in barley malt, we tried to express recombinant protein Z (rPZ) in E. coli. The present study aims to undertake a comparative analysis between natural PZ and rPZ in order to elucidate their respective characteristics. After spectral analysis, there are significant differences in their secondary and tertiary structures. In addition, rPZ showed superior foamability and foam stability. As for the serpin-like activity, the inhibition rate of rPZ is much higher than that of PZ. In contrast with the inhibition activity, the digestability of rPZ is much lower than that of PZ. As for the cargo carrier properties, rPZ showed an excellent ability to stabilize astaxanthin at 37 °C. These results suggest that rPZ is more suitable as protein carrier, due to the high foamability, serpin-like activity and low digestive stability, which not only give a brief view of recombinant protein, but also give a direction for PZ in cargo delivery.

2024-09-01·Biochemical Pharmacology

Aspirin alleviates fibronectin-induced preeclampsia phenotypes in a mouse model and reverses fibronectin-mediated trophoblast invasiveness under hypoxia by regulating ciliogenesis and Akt and MAPK signaling

Article

作者: Tsai, Pei-Yin ; Su, Mei-Tsz ; Lee, Chih-I ; Tam, Hoi-Lam

The placenta experiences a low-oxygen stage during early pregnancy. Aspirin is an effective preventative treatment for preeclampsia if applied early in pregnancy. Elevation of fibronectin (FN) level has been reported to be associated with preeclampsia; however, the role of FN in the physiological hypoxic phase and whether aspirin exerts its effect on FN at this hypoxic stage remain unknown. We determined pregnancy outcomes by injecting saline or recombinant FN protein into C57BL/6 pregnant mice and one group of FN-injected mice was fed aspirin. The effects of FN, the underlying pathways on trophoblast biology, and cilia formation under hypoxia were investigated in FN-pretreated or FN-knockdown HTR-8/SVneo cells in a hypoxic chamber (0.1 % O₂). Preeclampsia-like phenotypes, including blood pressure elevation and proteinuria, developed in FN-injected pregnant mice. The fetal weight of FN-injected mice was significantly lower than that of non-FN-injected mice (p < 0.005). Trophoblast FN expression was upregulated under hypoxia, which could be suppressed by aspirin treatment. FN inhibited trophoblast invasion and migration under hypoxia, and this inhibitory effect occurred through downregulating ZEB1/2, MMP 9 and the Akt and MAPK signaling pathways. Ciliogenesis of trophoblasts was stimulated under hypoxia but was inhibited by FN treatment. Aspirin was shown to reverse the FN-mediated inhibitory effect on trophoblast invasion/migration and ciliogenesis. In conclusion, FN overexpression induces preeclampsia-like symptoms and impairs fetal growth in mice. Aspirin may exert its suppressive effect on FN upregulation and FN-mediated cell function in the hypoxic stage of pregnancy and therefore provides a preventative effect on preeclampsia development.

2005-12-15·Cancer Research1区 · 医学

Headpin: A Serpin with Endogenous and Exogenous Suppression of Angiogenesis

1区 · 医学

Article

作者: Henderson, Ying ; Jayakumar, Arumugam ; Frederick, Mitchell ; Mazumdar, Abhijit ; Chattopadhyay, Chandrani ; Briggs, Katrina ; Clayman, Gary L. ; Shellenberger, Thomas D. ; Wang, Mary

AbstractHeadpin is a novel serine proteinase inhibitor (serpin) with constitutive mRNA expression in histologically normal oral mucosa but with lost or down-regulated expression in head and neck squamous cell carcinoma. Several serpin family members are similarly lost in multiple cancer types and hold tumor suppressor functions including the inhibition of angiogenesis. However, the functional significance for the loss of headpin expression in cancer is not known. Using immunohistochemical analysis of invasive squamous cell carcinoma and matched normal squamous mucosa of patient specimens, headpin expression was lost or down-regulated in the vast majority of tumor specimens. We investigated the functions of exogenous recombinant headpin and endogenously expressed headpin related to angiogenesis. In a rat corneal assay of neovascularization, recombinant headpin protein blocked in vivo angiogenesis mediated by interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF). In assays of cellular events in angiogenesis, headpin blocked the invasion, migration, and tube formation of endothelial cells. In light of our findings of nuclear subcellular localization of headpin, we investigated the expression and secretion of angiogenic factors and found reduced mRNA, protein, and promoter activities of IL-8 and VEGF. Finally, using a murine flank tumor model, headpin expression reduced growth and microvessel density in tumors derived from headpin-expressing UMSCC1 cells relative to those from vector control cells. These findings of nuclear regulatory functions of a serpin in the inhibition of angiogenesis bring new understanding to the cellular and molecular mechanisms of serpins. Therefore, this novel serpin targets diverse mechanisms against tumor angiogenesis on which to base therapeutic strategies. (Cancer Res 2005; 65(24): 11501-9)

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